Journal Article

Effects of Mesenchymal Stem Cell Transplantation on Cerebrospinal Fluid Biomarkers in Progressive Multiple Sclerosis

Karussis, Dimitrios, Petrou, Panayiota, Ginzberg, Ariel, Hallimi, Michelle, Kassis, Ibrahim

2022

Overview

Abstract Background Neurofilament light chains (NF-L) were shown to serve as a reliable biomarker of neurodegeneration in multiple sclerosis (MS). The chemokine receptor CXCL13 was shown to correlate with CNS inflammatory activity and to predict the future progression of MS. Objective To evaluate the levels of NF-L and CXCL13 in the cerebrospinal fluid (CSF) following treatment with mesenchymal stem cells (MSC) in patients with progressive MS. Methods The CSF samples were obtained from 48 patients with progressive MS who participated in a double-blind randomized phase II clinical trial that tested the effects of intrathecal (IT) or intravenous (IV) transplantation of mesenchymal stem cells (MSC), at baseline (before the first injection of the MSC) and at 6 months following treatment with MSC, or sham treatment. The CSF specimens were tested in a blinded way, using a single-molecule array (SIMOA) technique. Findings The CSF levels of NF-L were significantly lower at 6 months following treatment with MSC-IT when compared with the baseline, pre-treatment measurements (P = .026, Wilcoxon paired test). Nine out of 15 tested patients in the MSC-IT group had a reduction in NF-L levels of more than 50% (median decrease: −4449 pg/mL) when compared with 5/15 in the MSC-IV group (median decrease: −151 pg/mL) and 1/15 in the placebo group (median increase: +2450 pg/mL) (P = .001 for MSC-IT vs. placebo, chi-square test). CXCL13 levels were also reduced at 6 months following MSC-IT treatment but not to a statistically significant level. Conclusions Our findings indicate possible neuroprotective effects of MSC transplantation in patients with MS. Clinical trial registration NCT02166021

• Publisher: Oxford University Press
• Subject: Biomarkers / Brief Report / Cerebrospinal fluid / Chemokine receptors / Clinical trials / CXCL13 protein / Humans / Light chains / Mesenchymal Stem Cell Transplantation - methods / Mesenchymal Stem Cells / Multiple sclerosis / Multiple Sclerosis - therapy / Multiple Sclerosis, Chronic Progressive - cerebrospinal fluid / Multiple Sclerosis, Chronic Progressive - therapy / Neurodegeneration / Neuroprotection / Patients / Placebos / Statistical analysis / Stem cell transplantation / Stem cells